Immunology Flashcards
what reaction is allergy
type 1 hypersensitivity
IgE mediated
what is atopy
genetic tendency to produce specific IgE abs on exposure to common environmental antigens
tendency to develop IgE sensitisation
what allergic sx do food allergies produce
oral itching, tingling, hives
bronchospasm, wheezeing, laryngeal oedema
anaphylaxis
what happens in a type 1 hypersensitivity reaction
IgE attaches to Fc epsilon receptors on mast cells
cross linkage of bound specific IgE by allergen -> degranulation of mast cells and the release of inflammatory mediators
what are the pre-formed mediators in mast cell degranulation
histamine
tryptase
heparin
rapid release
what are the synthesised mediators in mast cell degranulation
leukotrienes
prostaglandins
slow release
how else can mast cells be activated
direct binding of radiocontrast dye, opiates to mast cell
what are the 3 cardinal features of acute allergic reactions and what mediates this
pruritus
vasodilation and leakage of fluid = hives, angioedema, hypotension
smooth muscle contraction = bronchospasm
HISTAMINE (acts on histamine receptors)
before planning allergy tests what is required for diagnosis of allergy
detailed clinical hx
what are the 2 methods of allergy testing
skin prick testing
blood tests - allergen specific IgE in serum
contraindications for skin prick testing
severe eczema
unable to stop antihistamines
on immune modulatory drugs
young children
what does a positive result mean in the skin prick tests and blood test
only confirms IgE sensitisation - may or may not be associated with clinical allergy (sx)
what are the blood test results for allergy measured in
kUA/L
what test must not be used as a screening test for allergy?
serum total IgE
why is serum tryptase useful for allergy testing
marker of mast cell degranulation
high levels after anaphylaxis
has a short half life - blood needs to be taken ASAP
if tryptase levels are chronically elevated what does this indicate
mastocytosis
what is the gold standard for allergy testing
double bind placebo control challenge
what is the basophil activation test
in vitro assay -activate patient basophils upon exposure to allergen and measure with flow cytometry
what is a true food allergy
IgE mediated de-granulation of mast cells.
Common food allergens: cow’s milk protein, egg, peanuts, tree nuts, fish, prawns
what is oral allergy syndrome
due to cross reacting ‘pan-allergens’ which are found in various members of the plant family (fruits, vegetables, nuts etc).
They are heat labile and destroyed by digestion, hence symptoms are usually limited to the oral cavity.
what is a false food allergy and what causes it
direct stimulation of mast cells or histamine ingestion Scombroid fish poisoning (scombrotoxicosis) – Histamine is released by bacterial action (spoilage) on scombroid fish (e.g tuna). Symptoms that mimic an allergic reaction occur
when the spoiled fish containing histamine is consumed.
what is food intolerance
adverse reaction to food, with no histamine related symptoms e.g Lactose intolerance, gluten sensitivity
investigations for suspected food allergy
base them on clinical hx
specific IgE blood tests or skin prick tests
what is eczema caused by
chronic skin condition
associated with filaggrin gene mutations
leads to poor barrier function of skin -> allows IgE sensitisation to aero-allergens and food allergens because of the thinner epidermis
what factors flare up eczema
microbes - infections
irritants - chemicals and soap
allergens - esp aero-allergens
other - temp, foods, stress
if someone has a true food allergy and eczema what can happen
eczema can flare up hours after allergic reaction
what is chronic spontaenous urticaria? (CSU)
common condition referred inappropriately to the Allergy clinic for ‘allergy testing’
characterised by the spontaneous occurrence of hives (urticaria), swellings (angioedema) or both, with daily or almost daily symptoms for at least 6 weeks
NOT IgE mediated
how is CSU diagnosed?
appearance and description of skin lesions with detailed clinical history
what causes CSU?
mast cell degranulation due to acute or chronic infections stress autoimmunity pseudo allergy to food and drugs
what makes CSU worse
Infections
• Stress
• Alcohol, caffeine, spices, food additives
• Hot showers, hot baths, overheating (duvets in bed)
• Tight clothing
• Medications Aspirin, Paracetamol, NSAIDS, ACE inhibitor, NB: Herbal/natural products
• Soaps, detergents, household products, skin creams and lotions
what is autoimmunity
breakdown in the mechanisms that maintain ‘self tolerance’ (elimination of self reactive cells)
leads to activation of self reactive clones of B and T cells
leads to generation of autoantibodies
do healthy individuals produce autoantibodies
yes - they help to remove products of tissue breakdown and clear up cell debris
low titre ANA are seen in absence of overt disease
what are autoimmune diseases
occurs when humoral and/or cell mediated responses to self antigen are associated with pathological changes
what are the 2 types of autoimmune diseases
organ specific
non-organ specific
examples of organ specific autoimmune diseases
MS Hashimoto's, thyroiditis, thyrotoxicosis myasthenia gravis pernicious anaemia Addison's disease insulin dependent DM
examples of non-organ specific autoimmune diseases
dermatomyositis
SLE
scleroderma
rheumatoid arthritis
what is autoimmune serology
identification and measurement of serum autoantibodies for diagnostic purposes
what are the methods of identification for autoantibodies
immunofluorescence, ELISA
what can a positive ANA test indicate
connective tissue disease - SLE, Sjorgen’s, sclerosis
rheumatoid arthritis and autoimmune thyroid disease
chronic infectious diseases (mononucleosis, hep C, bacterial endocarditis, TB)
drugs - hydralazine, isoniazid, anticonvulsives
what disease is associated with IgA Endomysial antibodies, IgA tTG antibodies
coeliac disease
what condition are Anti-glomerular basement membrane (GBM) Antibodies associated with
Goodpasture’s syndrome
what disease is associated with Anti-gastric parietal cell antibodies and Anti-intrinsic factor antibodies
pernicious anaemia
what antibodies is microscopic polyangitis associated with
Anti-MPO (p-ANCA)antibodies
what antibodies are phospholipid syndrome (Hughes) associated with
anti-cardiolipin antibodies
what conditions has Anti SSA (Ro) & Anti SSB(La) antibodies
Sjorgen’s syndrome
what antibodies are associated with rheumatoid arthritis
Anti- cyclic citrullinated peptide (CCP) antibodies (not rheumatoid factor)
clinical presentation of Sjogren’s/Sicca syndrome
female (50) decrease in secretions dry itchy irritated eyes dry mouth dental problems due to lack of saliva difficulty swallowing joint pain muscle aches low mood irritability impaired concentration fatigue
clinical presentation of SLE
skin (photosensitivity, rashes), joints (pain and swelling often affecting small joints) and organs (including kidneys, lungs, and brain)
clinical presentation of phospholipid syndrome
can occur in SLE patients high risk of blood clots recurrent miscarriages arterial/venous thrombosis livedo reticularis thrombocytopenia
clinical presentation of coeliac disease
diarrhoea abdominal pain bloating flatulence associated with type 1 DM dermatitis herpetiformis (blistering on elbows)
clinical presentation of myasthenia gravis
muscle weakness, commonly affecting muscles controlling the eyes and eyelids, facial expression, chewing, swallowing, and speaking
MG may also affect muscles of the arms, legs, neck, and respiratory muscles
antibodies associated with granulomatosis with polyangitis (GPA or Wegener’s granulomatosis)
Anti-PR3 (c-ANCA) antibodies
clinical presentation of GPA or wegener’s granulomatosis
flu like sx (prodromal syndrome associated with ENT problems)
followed by renal failure
what are primary systemic vasculitides
group of clinical disorders characterised by inflammation of blood vessels causing ischaemia and organ damage
commonly multi system involvement - as inflammation can involve several vascular beds -> renal failure, pulmonary haemorrhage
what investigations are ordered for suspected vasculitis
blood test biopsy angiography antibody tests - ANCA, GBM serum cryoglobulins complement
what are the large vessel vasculitis?
Giant cell arteritis
Takayasu arteritis
what are the medium vessel vasculitis?
- Polyarteritis nodosa
* Kawasaki disease
how can small vessel vasculitis be categorised
ANCA associated vasculitis
immune complex small vessel vasculitis
what are the ANCA associated small vessel vasculitis
Granulomatosis with Polyangiitis (GPA) formerly Wegener’s Granulomatosis
Microscopic Polyangiitis (MPA)
Eosinophilic Granulomatosis with Polyangiitis (EGPA) formerly Churg- Strauss syndrome
what are the immune complex small vessel vasculitis
- Anti-GBM disease (Goodpasture’s syndrome)
- Cryoglobulinaemic vasculitis
- IgA vasculitis (Henoch-Schonlein)
- Hypocomplementaemic urticarial vasculitis
which is the most common small vessel vasculitis
Granulomatosis with Polyangiitis (GPA) -formerly ‘Wegener’s granulomatosis
what are the 2 forms of granulomatosis with polyangitis
generalised form - pulmonary involvement may manifest as breathlessness; renal involvement manifests as (crescentic) glomerulonephritis
localised form - limited to the upper respiratory tract with chronic sinusitis, nasal crusting and/or recurrent epistaxis
what is the purpose of immunology testing
aids in clinical diagnosis
severity of disease
prognosis of disease
monitoring - disease activity, treatment, relapse, remission
what detection method is used for ANA testing
immunoflourescne or ELISA
what additional tests do you perform after positive ANA test
abs to DNA by ELISA (confirms ds-DNA) = crithidia test
abs to ENA - SSA (R0), SSB (La), RNP, Sm, Scl-70, Jo-1
what are the 2 classes of immune deficiency?
primary and secondary
what is primary immune deficiency due to
an immunological defect (usually genetic)
very rare
what is secondary immune deficiency due to
another disease drugs - immunosuppresssants, chemo, steroids myeloma, CLL nephrotic dyndrome AIDS protein losing enteropathy
what cells make up the innate immune system
neutrophils
macrophages
complement
what cells make up the adaptive immune system
B cells and antibodies
T cells
list 5 examples of primary immune deficiency
common variable immune deficiency (CVID) C1 esterase inhibitor deficiency/hereditary angioedema (HAE) X-linked agammaglobulinaemia (XLA) severe combined immune deficiency (SCID) chronic granulomatous disease (CGD)
what are the 6 hallmarks of primary immune deficiency (not HAE)
recurrent serious unusually persistent resistant to treatment unusual organisms unusual spread
what are the 10 warning signs of primary immunodeficiency
- > =4 new ear infections within 1 year
- > = 2 serious sinus infections within 1 year
- > = 2 months of abx with little/no affect
- > =2 pneumonias per year
- failure of infant to gain weight or grow normally
- recurrent, deep skin or organ abscesses
- persistent thrush in mouth or elsewhere on skin after 1 year of age
- requires IV abx to clear infections
- > =2 deep seated infections
- fhx of primary immune deficiency
what pathogens would we expect to see in a T cell defect?
pneumocystis
severe fungal/viral infections
HIV
what pathogens would we expect to see in a B cell or complement defect?
encapsulated bacteria
strep pneumoniae
haemophilius influenzae
what pathogens would we expect to see if neutrophils were defective
staph
serratia
klebiseilla
aspergillus
what pathogens would we expect to see if there was complement deficiency only
recurrent neisserial infections
meningitis, gonorrhoea
what are patients with primary immune deficiency more predisposed to?
autoimmune diseases (deficiency in one section can lead to overactivity in another)
malignancies
granulomatous disease
what are the 2 complications of diagnosing a primary immune deficiency late
1) irreversible structural damage which can be prevented by early treatment (bronchiectasis, give IV Ig)
2) life threatening laryngeal oedema which can be prevented by appropriate treatment (C1 esterase inhibitor deficiency = hereditary angioedema)
what are the initial screening tests for PID?
FBC - total lymphocyte and neutrophil count
Serum Igs - IgG, IgA, IgM
Complement - C3 & C4
what additional tests can be offered after initial screening and history for suspected PID
Specific antibodies to tetanus, haemophilius, pneumococcus (vaccine levels)
Lymphocyte subsets (T cells - CD4, CD8) , B cells, NK cells
C1 esterase inhibitor
NBT test for neutrophil oxidative burst
how would someone with common variable deficiency present
problem with abs made - require Ig replacement therapy
young adult - male or female
recurrent bacterial infections affecting lungs, sinuses, ears
has autoimmune diseases - idiopathic thrombocytopenic purpura, autoimmune haemolytic anaemia
possible signs of end organ damage such as bronchiectasis
what screening test would you request for CVID and what result would you expect
serum immunoglobulins
low IgG, low IgA and low/normal IgM
what other tests could be requested for suspected CVID diagnosis
IgG subclasses
antibodies to haemophilius
lymphocyte phenotyping - normal B and T cells
normal lymphocyte functioning
how does X-linked agammaglobulinaemia present
affects male infants only (as passed on by mother)
Recurrent bacterial infections of lungs, ears, gut
what are the typical results we would expect to see in someone with X-linked agammaglobulinaemia
low IgG, IgA, IgM
low total lymphocyte count
low/absent B lymphocytes - problem with the B cells (as very low Igs)
normal T lymphocytes
BTK gene mutations
what is severe combined immunodeficiency
paed medical emergency
B and T cell disorder
what is the typical presentation for SCID
young infant/baby
faltering growth
diarrhoea
severe candidiasis (fungus)
what results would you expect to see in a SCID patient
lymphocyte levels undetectable
both B and T cell very low
low Igs
what age do children get their full levels of Igs?
2 years
IgG can be higher though as get them through the placenta from mother and breast milk
what is hereditary angioedema and what is it a deficiency in
autosomal dominant condition associated with low plasma levels of the C1 inhibitor
leads to uncontrolled release of bradykinin resulting in oedema of tissues
C1 esterase inhibitor deficiency
there is a defect in complement (innate immune system) - complement has inhibitors as powerful system
lack of C1 inhibitor leads to complement always being switched on -> low C4 (being used up)
what is the clinical presentation for someone with suspected hereditary angioedema
recurrent, episodic, non-pitting circumscribed oedema (no urticaria) - often mistaken for anaphylaxis in A&E
unpredictable acute attacks at any body location - face, larynx, tongue, GIT, GUT, hand or arm, leg or foot
what screening tests would you order for hereditary angioedema and what would the results be
complement components C3 & C4
low C4, normal C3
then confirm by requesting C1 esterase inhibitor (see low levels)
what is the treatment for hereditary angioedema
C1 esterase inhibitor by infusion
what is chronic granulomatous disease
defects in proteins involved in oxidative burst of neutrophils/phagocytes (lack of NADPH oxidase)
what is the typical presentation for chronic granulomatous disease
recurrent pneumonias
recurrent abscesses due to bacteria and fungi (s aureus, aspergillus, klebsiella)
delayed healing
leads to oesophageal strictures (see on barium swallow)
what test results would we order for chronic granulomatous disease and what results would we expect
FBC - low Hb, normal lymphocytes, elevated neutrophils, elevated ESR
Serum Igs elevated
Raised CRP
Normal neutrophil phagocytosis
Absent neutrophil respiratory burst
